Stem-cell transplant wipes out HIV

But the treatment is too risky to help most who are infected with the virus.

A man may have been cured of both HIV and leukaemia after receiving a stem-cell transplant from a donor who is genetically
resistant to HIV.

About two years after the procedure, there is still no sign of the virus, even though the patient no longer takes antiretroviral
drugs. Nature News takes a look at the promises and limitations of the experimental treatment.

Haven't we heard about this before?

The German physicians announced their finding in November 2008. Since then, the results have been peer reviewed and are now published in the New England Journal of Medicine1.

What did the physicians actually do?

They essentially did what they would do for any leukaemia patient who was not responding adequately to chemotherapy: they
searched donor registries for bone-marrow donors who were a match for their patient, and prepared to perform a transplant.

But haematologist Gero Hütter of the Charité Universitätsmedizin in Berlin took the search for a donor one step further. Hütter
does not specialize in HIV cases but when he realized that his patient would need a transplant, he remembered a paper he had
read more than a decade earlier about HIV resistance in people who carry a specific genetic mutation.

The mutation is a short deletion in the CCR5 gene. The gene encodes a receptor that HIV uses to enter immune cells called CD4+ T cells. About 1% of the European population carries the CCR5 mutation in both copies of the CCR5 gene, making such people much less likely to contract the virus. If Hütter could replace his patient's immune cells with
cells that lacked the CCR5 receptor, his patient might be less susceptible to HIV infection.

The patient had 80 matches in the bone-marrow registries of the German Bone Marrow Donor Center, and Hütter reasoned that
one of those matches might also carry CCR5 mutations. Donor number 61 turned out to be the one, and in February 2007, the
transplant was performed.

Can we really learn anything from an experiment performed in only one patient?

Even though the technique has only been applied in one patient, the results are valuable, says James Riley, an HIV researcher
at the University of Pennsylvania in Philadelphia. "Of all the 'n=1' experiments out there, this is a good one," he says.
"It's a tremendous proof of principle that if you can make the majority of your cells resistant to infection, you can really
stop the virus."

Meanwhile, Hütter says that a different team of physicians intends to perform the same procedure in another HIV-positive patient
with leukaemia. So in a few years, the experiment may reach n=2.

Was the patient cured?

That remains unclear. Although the patient has gone about two years without a relapse, it is still possible that the virus
will make a comeback. The virus could be lurking in cells that doctors have not been able to test — such as cells in the brain
or heart.

In addition, there is another strain of HIV that does not use CCR5 receptors to invade cells. This strain does not typically
show up in patients with functioning immune systems, but it is still possible that this form of HIV could eventually proliferate
in this patient.

What is clear is that this is not a treatment most HIV-positive people would want to receive. The risks involved with a bone-marrow
transplant far outweigh those that come with years of antiretroviral drug therapy, even considering the troublesome side effects
of these drugs. Before receiving the transplant, recipients are "conditioned" with drugs and radiation to destroy their own
blood-producing stem cells. The procedure leaves them vulnerable to infection, and there is also the possibility that their
bodies will eventually reject the transplant.

Instead of risking a transplant, couldn't you just use a drug to block CCR5?

You could. One CCR5 inhibitor, called maraviroc, is made by the pharmaceutical company Pfizer and is approved for use in the
United States and Europe. Other companies are busy developing additional CCR5-targeting drugs.

Unfortunately, maraviroc does not completely prevent the virus from binding to CCR5, and it can only be used in combination
with other antiretrovirals. "Basically HIV can find its way around the drug and still use CCR5," says Riley, who adds that
the virus might outcompete the inhibitor, or may be able to bind to a different region of CCR5 than the drug.

Others are trying gene-therapy approaches to prevent CCR5 from being made at all. For example, Riley has been collaborating
with Sangamo BioSciences, a biotechnology company based in Richmond, California, to determine whether the company's technique
for snipping out targeted genes could be used to delete the CCR5 gene. Sangamo announced last week that it has launched a
Phase I clinical trial that will involve removing a sample of the participant's T cells, deleting the CCR5 gene, and then
infusing the cells back into the patient. The trial is a first step towards ascertaining the safety of the technique — not
its efficacy — and participants will not be conditioned to destroy their unmodified T cells.